FDA ( Food and Drug Administration ) approved Pegasys ( Peginterferon alfa-2a ) for the treatment of chronic hepatitis B ( CHB ).

Pegasys is the first and only pegylated Interferon approved for the treatment of chronic hepatitis B, including both variations of the virus - HBeAg-positive and HBeAg-negative chronic hepatitis B.

CDC ( Centers for Disease Control and Prevention ) estimates that 1.25 million people in the United States are chronically infected with hepatitis B.
Chronic hepatitis B can lead to cirrhosis, hepatocellular carcinoma and death.

In the U.S., the most common modes of transmission of the hepatitis B virus are through sexual and blood-to-blood contact, although the disease can also be transmitted from pregnant women to their infants.

The number of new infections in the U.S. has decreased in recent years, in part due to the introduction of the hepatitis B vaccine in 1982.
Almost all ( 90-95 percent ) adults who contract hepatitis B clear the virus from their systems within a few months and develop immunity.
The remainder of the infections become chronic, which is when the virus stays in the blood, infecting liver cells and possibly damaging them.

Pegasys was approved in 2002 by the FDA for use alone and in combination with Copegus ( Ribavirin ) for the treatment of adults with chronic hepatitis C ( CHC ).
In February 2005, Pegasys became the first and only FDA-approved therapy alone and in combination with Copegus for the treatment of chronic hepatitis C in patients coinfected with hepatitis C and HIV whose HIV is clinically stable.

Pegasys has a dual mode of action; it slows replication of the hepatitis B virus and boosts the immune system.

The two large-scale multinational phase III trials, in more than 1,500 patients with both the HBeAg-positive and HBeAg-negative variations of chronic hepatitis B, demonstrated that 24 weeks after a defined 48 week period of therapy, more patients achieved a sustained response with Pegasys than with Lamivudine.
These studies demonstrated that the addition of Lamivudine to Pegasys did not improve response rates over Pegasys alone.

Specifically, hepatitis B patients treated with Pegasys had higher rates of:

- HBV seroconversion in HBeAg positive patients ( 32% Pegasys vs. 19% Lamivudine )

- HBV DNA response ( 32% Pegasys vs. 22% Lamivudine in HBeAg positive patients and 43% Pegasys vs. 29% Lamivudine in HBeAg negative patients )

- ALT normalization in HBeAg negative patients ( 59% Pegasys vs. 44% Lamivudine ).

Conclusions regarding comparative efficacy of Pegasys and Lamivudine treatment based upon the end of follow-up results are limited by the different mechanisms of action of the two compounds.
Most treatment effects of Lamivudine are unlikely to persist 24 weeks after therapy is withdrawn.

Recent results from a long-term follow up study presented at the annual Meeting of the European Association for the Study of the Liver ( EASL, April 13-17, 2005 ) indicate that patients with HBeAg-negative chronic hepatitis B who responded to treatment with Pegasys maintained the benefit for at least a year after treatment.

The phase III study results in HBeAg-negative chronic hepatitis B were published in September 2004 in the New England Journal of Medicine.
The results of the phase III study in patients with HBeAg-positive chronic hepatitis B were presented at the 2004 annual meeting of EASL.
Lead investigators of both studies stated that the results of the trials warrant Pegasys becoming a first-line treatment for HBeAg-positive and HBeAg-negative chronic hepatitis B.

Alpha interferons, including Peginterferon alfa-2a, may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations.
Therapy should be withdrawn in patients with persistently severe or worsening signs or symptoms of these conditions.
In many, but not all cases, these disorders resolve after stopping Pegasys therapy.

Pegasys is contraindicated in patients with hypersensitivity to Pegasys or any of its components, autoimmune hepatitis, and hepatic decompensation ( Child-Pugh score greater than 6; class B and C ) in cirrhotic CHC monoinfected patients before or during treatment.
Pegasys is also contraindicated in hepatic decompensation with Child-Pugh score greater than or equal to 6 in cirrhotic CHC patients coinfected with HIV before or during treatment.
Pegasys is also contraindicated in neonates and infants because it contains benzyl alcohol. Benzyl alcohol is associated with an increased incidence of neurological and other complications in neonates and infants, which are sometimes fatal.

Source: Roche, 2005


XagenaMedicine2005